In vivo 31-P nuclear magnetic resonance (NMR) techniques have been used to evaluate the effects of several toxic substances on tissue metabolism, with particular emphasis on the potential significance of changes in the levels of non-cyclic phosphodiesters. In mammalian systems, the phosphodiesters glycerophosphoryl choline (GPC) and glycerophosphoryl ethanolamine (GPE) are readily observed in many tissues and hence are present at near millimolar levels. Although most generally postulated to be lipid catabolites, it is difficult to reconcile this lack of function with the high tissue levels observed. Further, the presence of analogous phosphodiesters such as serine ethanolamine phosphodiesters (SEP) which is found in the chicken, and threonine ethanolamine phosphodiester (TEP) which we have found to be the major phosphorus-containing metabolite in fish lens, also suggests functions beyond that of lipid breakdown product. Studies on the effects of acute arsenite poisoning using surface coil 31-P NMR spectroscopy on the liver of anesthetized rats indicate significant time-dependent increases in the levels of both GPC and GPE. These changes are consistent with an increase in lysophospholipase activity in response to the arsenite. Studies of the effects of chronic vanadium administration to chickens using surface coil observation of muscle tissue failed to indicate any significant changes in the SEP levels, although pH changes consistent with the inhibition of the Na/K ATPase were noted. Further studies designed to unravel the potential role of non-cyclic phosphodiesters in the regulation of lipid metabolism are in progress.